α-halo-α,β-unsaturated aldehydes/ketones, which are also known in the art as α-halo enals/enones, are versatile intermediates in the field of organic synthesis. While these compounds are very attractive to synthetic chemists, synthesizing these substrates has proven to be challenging and lacking in overall efficiency.
Prior methods to produce α-iodo enals, for example, have shown to be deficient because they may require multiple steps, require strong conditions, or may be limited in substrate scope. By way of example, an α-iodo enal may be synthesized from propanediol over a lengthy five-step sequence: (1) a mono-protection of the diol, (2) an oxidation of the free hydroxyl group to the aldedyde, (3) a Horner-Emmons reaction using in situ-generated triethyl iodophosphonoacetate, (4) a reduction of the ester to the alcohol, and (5) an oxidation of the alcohol to the aldehyde. See Shibahara, S.; Fujino, M.; Tashiro, Y.; Takahashi, K.; Ishihara, J.; Hatakeyama, S. Org. Lett. 2008, 10, 2139-2142. In another example, treating a propargyl alcohol derivative with aqueous hydroiodic acid in toluene provides an iodoallene intermediate, which can be oxidized with molecular oxygen to yield the α-iodo enal. See Chen, S.; Wang, J. J. Org. Chem. 2007, 72, 4993-4996. In yet another example, propargyl alcohol derivatives may be treated with iodine, followed by oxidation with over two equivalents of pyridinium dichromate to provide the α-iodo enal. See Antonioletti, R.; D'Auria, M.; Piancatelli, G.; Scettri, A. Tetrahedron Lett, 1981, 22, 1041-2.
Recently, it has been shown that α-halo-α,β-unsaturated aldehydes and ketones may be prepared from propargyl acetates under catalytic conditions. While catalytic reactions are generally considered efficient, this methodology requires a propargyl ester precursor, i.e., an acetate group on the propargyl hydroxyl group, and is understood to be limited in scope. See Yu, M.; Zhang, G.; Zhang, L. Org. Lett. 2007, 9, 2147-2150. Accordingly, there is still a need in the art for a simple and efficient, catalytic method of synthesizing a broad variety of α-halo-α,β-unsaturated aldehydes and ketones.